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Review

Pathological and clinical aspects of alpha/beta synuclein in Parkinson’s disease and related disorders

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Pages 505-513 | Received 04 Feb 2016, Accepted 08 Mar 2016, Published online: 25 Mar 2016

References

  • Dehay B, Bourdenx M, Gorry P, et al. Targeting α-synuclein for treatment of Parkinson’s disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855–866.
  • Sekigawa A, Takamatsu Y, Sekiyama K, et al. Role of - and Synucleins in the axonal pathology of Parkinson’s Disease and related synucleinopathies. Biomolecules. 2015;5:1000–1011.
  • Lashuel HA, Overk CR, Oueslati A, et al. The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2013;14(1):38–48.
  • Braak H, Braak E. Pathoanatomy of Parkinson’s disease. J Neurol. 2000;247(Suppl 2):II3–10.
  • Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276(5321):2045–2047.
  • Surguchov A. Synucleins: are they two-edged swords? J Neurosci Res. 2013;91(2):161–166.
  • George JM. The synucleins. Genome Biol. 2002;3(1): Reviews 3002.1-6
  • Bendor JT, Logan TP, Edwards RH. The function of α-synuclein. Neuron. 2013;79(6):1044–1066.
  • Xia Y, Saitoh T, Uéda K, et al. Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms. J Alzheimers Dis. 2001;3(5):485–494.
  • Uéda K, Fukushima H, Masliah E, et al. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90(23):11282–11286.
  • Waxman EA, Giasson BI. Molecular mechanisms of α-synuclein neurodegeneration. Biochim Biophys Acta. 2009;1792(7):616–624.
  • Giasson BI, Murray IV, Trojanowski JQ, et al. A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J Biol Chem. 2001;276(4):2380–2386.
  • Kalia LV, Kalia SK, Lang AE. Disease-modifying strategies for Parkinson’s disease. Mov Disord. 2015;30(11):1442–1450.
  • Kim H-J. Alpha-synuclein expression in patients with Parkinson’s Disease: a clinician’s perspective. Exp Neurobiol. 2013;22(2):77–83.
  • Vekrellis K, Xilouri M, Emmanouilidou E, et al. Pathological roles of α-synuclein in neurological disorders. Lancet Neurol. 2011;10(11):1015–1025.
  • Quist A, Doudevski I, Lin H, et al. Amyloid ion channels: a common structural link for protein-misfolding disease. Proc Natl Acad Sci USA. 2005;102(30):10427–10432.
  • Danzer KM, Haasen D, Karow AR, et al. Different species of alpha-synuclein oligomers induce calcium influx and seeding. J Neurosci. 2007;27(34):9220–9232.
  • Van Rooijen BD, Claessens MM, Membrane SV. Permeabilization by oligomeric α-synuclein: in search of the mechanism. PLoS One. 2010;5(12):e14292.
  • Kalia LV, Kalia SK, McLean PJ, et al. α-Synuclein oligomers and clinical implications for Parkinson disease. Ann Neurol. 2013;73(2):155–169.
  • Lavedan C, Leroy E, Torres R, et al. Genomic organization and expression of the human beta-synuclein gene (SNCB). Genomics. 1998;54(1):173–175.
  • Brighina L, Okubadejo NU, Schneider NK, et al. Beta-synuclein gene variants and Parkinson’s disease: a preliminary case-control study. Neuroscience Let. 2007;420(3):229–234.
  • Hashimoto M, Rockenstein E, Mante M, et al. beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron. 2001;32(2):213–223.
  • Hashimoto M, Rockenstein E, Mante M, et al. An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model. Gene Ther. 2004;11(23):1713–1723.
  • Shaltiel-Karyo R, Frenkel-Pinter M, Egoz-Matia N, et al. Inhibiting α-synuclein oligomerization by stable cell-penetrating β-synuclein fragments recovers phenotype of Parkinson’s disease model flies. PLoS One. 2010;5(11):e13863.
  • Ninkina NN, Alimova-Kost MV, Paterson JW, et al. Organization, expression and polymorphism of the human persyn gene. Hum Mol Genet. 1998;7(9):1417–1424.
  • Chandra S, Fornai F, Kwon H-B, et al. Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc Natl Acad Sci U S A. 2004;101(41):14966–14971.
  • Greten-Harrison B, Polydoro M, Morimoto-Tomita M, et al. αβγ-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proc Natl Acad Sci U S A. 2010;107(45):19573–19578.
  • Masliah E, Hashimoto M. Development of new treatments for Parkinson’s disease in transgenic animal models: a role for beta-synuclein. Neurotoxicology. 2002;23(4–5):461–468.
  • Takenouchi T, Hashimoto M, Hsu LJ, et al. Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human alpha-synuclein. Mol Cell Neurosci. 2001;17(1):141–150.
  • Jensen PH. α-Synuclein/Amyloid Interactions. Methods Mol Med. 2001;62:61–65.
  • Park J-Y, Lansbury LPT. Beta-synuclein inhibits formation of alpha-synuclein protofibrils: a possible therapeutic strategy against Parkinson’s disease. Biochemistry. 2003;42(13):3696–3700.
  • Uversky VN, Li J, Souillac P, et al. Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins. J Biol Chem. 2002;277(14):11970–11978.
  • Windisch M, Hutter-Paier B, Schreiner E, et al. Beta-Synuclein-derived peptides with neuroprotective activity: an alternative treatment of neurodegenerative disorders? J Mol Neurosci. 2004;24(1):155–165.
  • Da Costa CA, Masliah E, Checler F. Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson’s disease. J Biol Chem. 2003;278(39):37330–37335.
  • Fan Y, Limprasert P, Murray IVJ, et al. Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression. Hum Mol Genet. 2006;15(20):3002–3011.
  • Pan GY, Liu XD, Liu GQ. Intracarotid infusion of hypertonic mannitol changes permeability of blood-brain barrier to methotrexate in rats. Acta Pharmacol Sin. 2000;21(7):613–616.
  • Shaltiel-Karyo R, Frenkel-Pinter M, Rockenstein E, et al. A blood-brain barrier (BBB) disrupter is also a potent α-synuclein (α-syn) aggregation inhibitor: a novel dual mechanism of mannitol for the treatment of Parkinson disease (PD). J Biol Chem. 2013;288(24):17579–17588.
  • Lindström V, Fagerqvist T1, Nordström E, et al. Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice. Neurobiol Dis. 2014;69:134–143.
  • Masliah E, Rockenstein E, Adame A, et al. Effects of alpha-synuclein immunization in a mouse model of Parkinson’s disease. Neuron. 2005;46(6):857–868.
  • Ghochikyan A, Petrushina I, Davtyan H, et al., Immunogenicity of epitope vaccines targeting different B cell antigenic determinants of human α-synuclein: feasibility study. Neurosci Lett. 2014;560:86–91.
  • Mandler M, Valera E, Rockenstein E, et al. Next-generation active immunization approach for synucleinopathies: implications for Parkinson’s disease clinical trials. Acta Neuropathol. 2014;127(6):861–879.
  • Shimamura M, Sato N, Morishita R. Sato N and Morishita R. Experimental and clinical application of plasmid DNA in the field of central nervous diseases. Current Gene Therapy. 2011;11(6):491–500.
  • Chen Z, Yang Y, Yang X, et al. Immune effects of optimized DNA vaccine and protective effects in a MPTP model of Parkinson’s disease. Neurol Sci. 2013;34(9):1559–1570.
  • Ugen KE, Lin X, Bai G, et al. Evaluation of an α synuclein sensitized dendritic cell based vaccine in a transgenic mouse model of Parkinson disease. Hum Vaccin Immunother. 2015;11(4):922–930.
  • Sanchez-Guajardo V, Barnum CJ, Tansey MG, et al. Neuroimmunological processes in Parkinson’s disease and their relation to α-synuclein: microglia as the referee between neuronal processes and peripheral immunity. ASN Neuro. 2013;5(2):113–139.
  • Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31–40.
  • Schneeberger A, Tierney L, Mandler M, Active immunization therapies for Parkinson’s disease and multiple system atrophy. Mov Disord. 2015. doi:10.1002/mds.26377 [Epub ahead of print]
  • Karuppagounder SS, Brahmachari S, Lee Y, et al. The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson’s disease. Sci Rep. 2014;4:4874.

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